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Lyme Disease

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Lyme Disease, Borrelia Burgdorferi, Lyme borreliosis

  • Epidemiology
  1. Incidence
    1. Most common tick borne disease in North America
    2. Cases in U.S. in 1994: 13,000
    3. Cases in U.S. in 1999: 16,000
    4. Cases in U.S. in 2006: 20,000
    5. Cases in U.S. in 2014: 19,985
    6. Annual Incidence in endemic areas: 0.5%
    7. Peak occurrence in North America: May to August
  2. Demographics
    1. Gender: Much more common in males
    2. Age: Bimodal peak distribution (ages 5-9 and 55-59 years old)
  3. Geographic areas involved
    1. Worldwide cases have occurred in Canada, Europe, Asia
    2. U.S. cases clustered in Northeast and Upper Midwest (90% of U.S. cases)
      1. High-Risk States
        1. Connecticut (Nantucket County: 1198 case/100,000)
        2. Delaware
        3. Maryland
        4. New Jersey
        5. New York
        6. Pennsylvania
        7. Rhode Island
        8. Wisconsin
      2. Moderate-Risk States
        1. Maine
        2. Massachusetts
        3. Minnesota
        4. New Hampshire
        5. Vermont
    3. Reference
      1. (1995) MMWR Morb Mortal Wkly Rep 44:459-62 [PubMed]
  4. Concurrent Lyme and Babesiosis is common (n=1156)
    1. Coinfection occurs 10% in southern New England
    2. Reference
      1. Krause (1996) JAMA 275:1657-60 [PubMed]
  • History
  1. 1975: Lyme Disease first reported in Lyme, Connecticut
    1. Cluster of new cases of Arthritis in children
  2. 1981: Borrelia Burgdorferi identified as cause
  • Pathophysiology
  1. Borrelia Burgdorferi
    1. Causative Spirochete organism
    2. Carried by white tail deer
    3. Transmitted by Deer Ticks
    4. Natural reservoirs
      1. White-footed mouse and other small mammals
  2. Deer Ticks or Black Legged Tick
    1. Vectors for several infections
      1. Borrelia Burgdorferi (Lyme Disease)
      2. Babesia microti (Babesiosis)
      3. Anaplasma phagocytophila (causes HGA)
        1. Prior: Ehrilichia phagocytophila (Ehrlichiosis)
    2. Tick species
      1. Ixodes Scapularis
      2. Ixodes pacificus (West coast)
  3. Deer Ticks have two year life cycle:
    1. Egg to Larva
    2. Larva to Nymph
    3. Nymph to Adult
  4. In endemic areas:
    1. Nymphs infected: 12-30%
    2. Adult ticks infected: 28-65%
  5. Nymphs outnumber adult ticks 10:1
    1. Nymphs are responsible for 90% of Lyme Disease cases
    2. Transmission relies on the time it takes for Borrelia to migrate from tick midgut to its Salivary Glands
      1. Nymphs must attach for >36-48 hours for transmission
      2. Adult ticks must attach for >48-72 hours for transmission
  • Differential Diagnosis
  1. Erythema Migrans
    1. See Annular Lesion
    2. Cellulitis
    3. Tinea Corporis
    4. Granuloma Annulare
    5. Arthropod Bite reaction
      1. Usually <5 cm, painful, develops in minutes to hours
      2. Rash is often pruritic
      3. Resolves within 48 hours without viral symptoms
  2. Other Ixodes tick (Deer Tick) borne infection
    1. Babesiosis
    2. Human Granulocytic Anaplasmosis
  • Signs and Symptoms
  • Stage 1 (Early localized disease)
  1. Less than 20% of people recall Tick Bite
  2. Localized Erythema Chronicum Migrans at Tick Bite site (present in 80% of cases)
    1. See Erythema Migrans
    2. Expanding red Macule or Papule
    3. Size 5 cm or greater (rapid and prolonged expansion is unique)
    4. Central clearing is variably present
  3. Mild constitutional Symptoms
    1. Fever (also consider HGA or Babesiosis)
    2. Malaise
    3. Arthralgias (esp. Monoarthritis of the knee or hip)
    4. Headache
    5. Neck stiff
    6. Other skin lesions
  • Signs and Symptoms
  • Stage 2 (Early disseminated disease)
  1. Cardiac (<10% of patients; onset typically within 1-2 months of infection)
    1. Atrioventricular Block (49% with third degree AV Block)
    2. Pericarditis
    3. Myocarditis
  2. Musculoskeletal
    1. Arthralgias
    2. Myalgias
  3. Neurologic
    1. Bell's Palsy (or other Cranial NerveNeuropathy)
      1. Strongly consider empiric treatment for Lymes Disease with Bell's Palsy in Lyme endemic regions
    2. Lymphocytic Meningitis or Encephalitis
    3. Pseudotumor Cerebri
  4. Ophthalmologic
    1. Conjunctivitis
    2. Iritis
  5. Urologic
    1. Microscopic Hematuria
    2. Proteinuria
  6. Miscellaneous
    1. Regional Lymphadenopathy or General Lymphadenopathy
    2. Multiple Erythema Migrans lesions (hematogenous spread of infection)
    3. Hepatitis
  • Signs and Symptoms
  • Stage 3 (Late chronic disease)
  1. Large Joint Arthritis (especially knees; hips may also be involved)
    1. Occurs in 10-60% of untreated Lyme Disease
    2. Arthritis presents at approximately 6 months after infection onset
    3. Monoarticular or asymmetric Oligoarticular Arthritis
  2. Neurologic (10-15% of untreated patients)
    1. See Stage 2 neurologic conditions
    2. Symptoms
      1. Altered Mental Status
      2. Headaches
      3. Neck Pain or stiffness
      4. Sudden Hearing Loss
    3. Classic triad
      1. Lymphocytic Meningitis
      2. Cranial Neuropathy (especially Bell's Palsy)
      3. Radiculoneuropathy
    4. Other manifestations
      1. Subacute encephalopathy
      2. Axonal Polyneuropathy
      3. Leukoencephalopathy
      4. Cerebellar Ataxia
      5. Mononeuritis multiplex
  • Labs
  • Two tiered protocol
  1. See Lyme Test
  2. Lyme Titer (ELISA) - first tier testing
    1. Not needed if Erythema Migrans in endemic areas
    2. False Positive Rate is high
    3. Positive results are reflexed to Western Blot for confirmation
  3. Lyme Western Blot
    1. Confirms Lyme Titer result
    2. False Negative in 60-75% of patients without disseminated disease
  • Labs
  • Other
  1. Synovial Fluid Lyme PCR
    1. Joint aspiration in cases of suspected Lyme Arthritis
  2. Cerebrospinal fluid (CSF) for Intrathecal Lyme Antibody production
    1. Indicated for neurologic symptoms
  3. C6 Peptide assay (IgG enzyme linked immunosorbent assay)
    1. Under study as of 2012 for replacement of the two tiered protocol
  • Labs
  • Precautions
  1. Lyme urine antigen
    1. High False Positive Rate and not recommended
  2. Borrelia Burgdorferi IgG and IgM
    1. Persists for years following effective antibiotic treatment
    2. Positive test after treatment does not indicate failed antibiotics or chronic infection
  • Labs
  • Tests to identify other causes
  • Differential Diagnosis
  1. See Tick-Borne Illness
  2. See Deer Tick
    1. In addition to Lyme Disease, Deer Ticks transmit Babesiosis and Human Granulocytic Anaplasmosis
  • Precautions
  1. Consider Lyme Disease in unexplained symptoms (Arthralgias, focal weakness) despite lack of bite history
    1. Fluctuating meningoencephalitis symptoms
    2. Cranial Nerve palsy (e.g. Bell's Palsy, especially if bilateral)
    3. Peripheral Neuropathy or radiculopathy
    4. New first-degree AV Block or dysrhythmia
    5. New left-ventricular dysfunction
  2. Information based on IDSA and CDC guidelines
    1. IDSA: Infectious Disease Society of America
    2. IDSA is considered standard of care recommendations
    3. Tertiary centers (e.g. Mayo) follow these guidelines
  3. Other guidelines (e.g. ILADS) are not reviewed here
    1. ILADS: International Lyme and Associated Diseases
    2. ILADS guidelines are considered controversial
  1. Antibiotic treatment risks Jarisch-Herxheimer type reaction (affects 15% of patients)
    1. Borrelia is a Spirochete with potential for similar reaction to antibiotics as for Syphilis
    2. Manifests as increased Temperature, myalgias and Arthralgias in first 24 hours of treatment
  2. Doxycycline (Avoid in pregnancy and under age 9 years)
    1. Preferred oral agent due to cross-coverage of other tick-borne infections
    2. Adult: 100 mg orally twice daily for 10 to 21 days (typically 14 days per CDC)
    3. Child (age >8): 4 mg/kg orally divided twice daily (max 100 mg/dose) for 10-21 days (typically 14 days per CDC)
  3. Amoxicillin
    1. Adult: 500 mg orally three times daily for 14 to 21 days (typically 21 days per CDC)
    2. Child: 50 mg/kg/day divided three times daily (max 500 mg/dose) for 14 to 21 days (typically 21 days per CDC)
  4. Cefuroxime (Ceftin)
    1. Adult: 500 mg orally twice daily for 14 to 21 days
    2. Child: 30 mg/kg/day divided twice daily (max: 500 mg/dose) for 14 to 21 days
  5. Macrolides have lower efficacy (consider other agents above if possible)
    1. Use only if allergic to above agents
    2. Azithromycin
      1. Adult: 500 mg daily for 10 days
      2. Child: 10 mg/kg daily for 10 days
    3. Clarithromycin
      1. Adult: 500 mg orally twice daily for 21 days
      2. Child: 7.5 mg/kg (max: 500 mg/dose) orally twice daily for 21 days
    4. Erythromycin
      1. Adult: 500 mg orally four times daily for 21 days
      2. Child: 12.5 mg/kg (max 500 mg/dose) orally four times daily for 21 days
  6. If suspect Cellulitis versus Erythema Migrans
    1. Augmentin 50 mg/kg/day divided bid or tid (up to 875 mg twice daily)
    2. Cefuroxime 30 mg/kg/day divided twice daily (up to 500 mg twice daily)
    3. Doxycycline 4 mg/kg divided twice daily (up to 100 mg twice daily)
  7. Antibiotics to avoid (not indicated)
    1. Avoid First Generation Cephalosporins (Cephalexin)
    2. Avoid Fluoroquinolones
    3. Avoid Septra, Metronidazole, Penicillin G
  • Management
  • Stage 2 (Early disseminated with cardiac or neurologic findings)
  1. Indications for hospitalization
    1. New first degree AV Block with PR >300 ms
    2. New second or third degree AV Block
    3. Chest Pain, Syncope or Dyspnea
    4. Lyme Meningitis
  2. Protocol
    1. Isolated Bell's Palsy may be treated with agents used for stage 1 - Erythema Migrans findings as above
    2. Obtain Lumbar Puncture for neurologic findings attributed to Lymes Disease
  3. Ceftriaxone (Rocephin)
    1. Adult: 2g/day IV for 14 to 21 days
    2. Child: 75-100 mg/kg/day IV for 14 to 21 days
  4. Cefotaxime (Claforan)
    1. Adult: 2g every 8 hours for 14 to 21 days
    2. Child: 150-200 mg/kg/day divided every 6 to 8 hours IV for 14-21 days
  5. Doxycycline (Avoid in pregnancy and under age 9 years)
    1. Adult: 200 to 400 mg orally divided twice daily for 10 to 28 days
    2. Child: 4 to 8 mg/kg orally divided twice daily for 10 to 28 days
  • Management
  • Stage 3 (Late Lyme Disease)
  1. Arthritis
    1. Use same oral antibiotic protocols as under Stage 1 - Erythema Migrans management
    2. Persistent or recurrent Joint Swelling despite initial antibiotics course
      1. Consider repeating a 4 week course of oral antibiotics or 2-4 week course of Ceftriaxone
  2. Neurologic findings
    1. Use same intravenous antibiotic protocols as under Stage 2 - early disseminated management
    2. Post-Lyme Disease syndrome of persistent Fatigue or cognitive difficulties
      1. No benefit to prolonged antibiotic courses or other medication management
      2. Klempner (2013) Am J Med 126(8):665-9 +PMID:23764268 [PubMed]
  • Prevention
  1. See Prevention of Vector-borne Infection
  2. See Antibiotic Prophylaxis After Known Deer Tick Bite
  3. Lyme Vaccine (No longer available in U.S.)
  4. Insecticide
    1. Acaricide applied to residential areas in mid May
    2. Provides 97% protection during peak nymph activity